Abstract
Oxygen radicals and nitric oxide (NO) are generated in excess in a diverse array of microbial infections. Emerging concepts in free radical biology are now shedding light on the pathogenesis of various diseases. Freeโradical induced pathogenicity in virus infections is of great importance, because evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases. Although oxygen radicals and NO have an antimicrobial effect on bacteria and protozoa, they have opposing effects in virus infections such as influenza virus pneumonia and several other neurotropic virus infections. A high output of NO from inducible NO synthase, occurring in a variety of virus infections, produces highly reactive nitrogen oxide species, such as peroxynitrite, via interaction with oxygen radicals and reactive oxygen intermediates. The production of these various reactive species confers the diverse biological functions of NO. The reactive nitrogen species cause oxidative tissue injury and mutagenesis through oxidation and nitration of various biomolecules. The unique biological properties of free radicals are further illustrated by recent evidence showing accelerated viral mutation by NOโinduced oxidative stress. NO appears to affect a host's immune response, with immunopathological consequences. For example, NO is reported to suppress type 1 helper T cellโdependent immune responses during infections, leading to type 2 helper T cellโbiased immunological host responses. NOโinduced immunosuppression may thus contribute to the pathogenesis of virus infections and help expansion of quasispecies population of viral pathogens. This review describes the pathophysiological roles of free radicals in the pathogenesis of viral disease and in viral mutation as related to both nonspecific inflammatory responses and immunological host reactions modulated by NO. Copyright ยฉ 2001 John Wiley & Sons, Ltd.